Bisphenol A induces otolith malformations during vertebrate embryogenesis

<p>Abstract</p> <p>Background</p> <p>The plastic monomer and plasticizer bisphenol A (BPA), used for manufacturing polycarbonate plastic and epoxy resins, is produced at over 2.5 million metric tons per year. Concerns have been raised that BPA acts as an endocrine disruptor on both developmental and reproductive processes and a large body of evidence suggests that BPA interferes with estrogen and thyroid hormone signaling. Here, we investigated BPA effects during embryonic development using the zebrafish and <it>Xenopus </it>models.</p> <p>Results</p> <p>We report that BPA exposure leads to severe malformations of the otic vesicle. In zebrafish and in <it>Xenopus </it>embryos, exposure to BPA during the first developmental day resulted in dose-dependent defects in otolith formation. Defects included aggregation, multiplication and occasionally failure to form otoliths. As no effects on otolith development were seen with exposure to micromolar concentrations of thyroid hormone, 17-ß-estradiol or of the estrogen receptor antagonist ICI 182,780 we conclude that the effects of BPA are independent of estrogen receptors or thyroid-hormone receptors. Na⁺/K⁺ATPases are crucial for otolith formation in zebrafish. Pharmacological inhibition of the major Na⁺/K⁺ATPase with ouabain can rescue the BPA-induced otolith phenotype.</p> <p>Conclusions</p> <p>The data suggest that the spectrum of BPA action is wider than previously expected and argue for a systematic survey of the developmental effects of this endocrine disruptor.</p

The Phytoestrogen Genistein Affects Zebrafish Development through Two Different Pathways

BackgroundEndocrine disrupting chemicals are widely distributed in the environment and derive from many different human activities or can also be natural products synthesized by plants or microorganisms. The phytoestrogen, genistein (4&prime;, 5, 7-trihydroxy-isoflavone), is a naturally occurring compound found in soy products. Genistein has been the subject of numerous studies because of its known estrogenic activity.Methodology/ Principal FindingsWe report that genistein exposure of zebrafish embryos induces apoptosis, mainly in the hindbrain and the anterior spinal cord. Timing experiments demonstrate that apoptosis is induced during a precise developmental window. Since adding ICI 182,780, an ER antagonist, does not rescue the genistein-induced apoptosis and since there is no synergistic effect between genistein and estradiol, we conclude that this apoptotic effect elicited by genistein is estrogen-receptors independent. However, we show in vitro, that genistein binds and activates the three zebrafish estrogen receptors ER&alpha;, ER&beta;-A and ER&beta;-B. Furthermore using transgenic ERE-Luciferase fish we show that genistein is able to activate the estrogen pathway in vivo during larval stages. Finally we show that genistein is able to induce ectopic expression of the aromatase-B gene in an ER-dependent manner in the anterior brain in pattern highly similar to the one resulting from estrogen treatment at low concentration.Conclusion/SignificanceTaken together these results indicate that genistein acts through at least two different pathways in zebrafish embryos: (i) it induces apoptosis in an ER-independent manner and (ii) it regulates aromatase-B expression in the brain in an ER-dependent manner. Our results thus highlight the multiplicity of possible actions of phytoestrogens, such as genistein. This suggests that the use of standardized endpoints to study the effect of a given compound, even when this compound has well known targets, may carry the risk of overlooking interesting effects of this compound.<br /

Altimetry for the future: Building on 25 years of progress

In 2018 we celebrated 25 years of development of radar altimetry, and the progress achieved by this methodology in the fields of global and coastal oceanography, hydrology, geodesy and cryospheric sciences. Many symbolic major events have celebrated these developments, e.g., in Venice, Italy, the 15th (2006) and 20th (2012) years of progress and more recently, in 2018, in Ponta Delgada, Portugal, 25 Years of Progress in Radar Altimetry. On this latter occasion it was decided to collect contributions of scientists, engineers and managers involved in the worldwide altimetry community to depict the state of altimetry and propose recommendations for the altimetry of the future. This paper summarizes contributions and recommendations that were collected and provides guidance for future mission design, research activities, and sustainable operational radar altimetry data exploitation. Recommendations provided are fundamental for optimizing further scientific and operational advances of oceanographic observations by altimetry, including requirements for spatial and temporal resolution of altimetric measurements, their accuracy and continuity. There are also new challenges and new openings mentioned in the paper that are particularly crucial for observations at higher latitudes, for coastal oceanography, for cryospheric studies and for hydrology. The paper starts with a general introduction followed by a section on Earth System Science including Ocean Dynamics, Sea Level, the Coastal Ocean, Hydrology, the Cryosphere and Polar Oceans and the ‘‘Green” Ocean, extending the frontier from biogeochemistry to marine ecology. Applications are described in a subsequent section, which covers Operational Oceanography, Weather, Hurricane Wave and Wind Forecasting, Climate projection. Instruments’ development and satellite missions’ evolutions are described in a fourth section. A fifth section covers the key observations that altimeters provide and their potential complements, from other Earth observation measurements to in situ data. Section 6 identifies the data and methods and provides some accuracy and resolution requirements for the wet tropospheric correction, the orbit and other geodetic requirements, the Mean Sea Surface, Geoid and Mean Dynamic Topography, Calibration and Validation, data accuracy, data access and handling (including the DUACS system). Section 7 brings a transversal view on scales, integration, artificial intelligence, and capacity building (education and training). Section 8 reviews the programmatic issues followed by a conclusion

BLOOM: A 176B-Parameter Open-Access Multilingual Language Model

Large language models (LLMs) have been shown to be able to perform new tasks based on a few demonstrations or natural language instructions. While these capabilities have led to widespread adoption, most LLMs are developed by resource-rich organizations and are frequently kept from the public. As a step towards democratizing this powerful technology, we present BLOOM, a 176B-parameter open-access language model designed and built thanks to a collaboration of hundreds of researchers. BLOOM is a decoder-only Transformer language model that was trained on the ROOTS corpus, a dataset comprising hundreds of sources in 46 natural and 13 programming languages (59 in total). We find that BLOOM achieves competitive performance on a wide variety of benchmarks, with stronger results after undergoing multitask prompted finetuning. To facilitate future research and applications using LLMs, we publicly release our models and code under the Responsible AI License

Altimetry for the future: building on 25 years of progress

In 2018 we celebrated 25 years of development of radar altimetry, and the progress achieved by this methodology in the fields of global and coastal oceanography, hydrology, geodesy and cryospheric sciences. Many symbolic major events have celebrated these developments, e.g., in Venice, Italy, the 15th (2006) and 20th (2012) years of progress and more recently, in 2018, in Ponta Delgada, Portugal, 25 Years of Progress in Radar Altimetry. On this latter occasion it was decided to collect contributions of scientists, engineers and managers involved in the worldwide altimetry community to depict the state of altimetry and propose recommendations for the altimetry of the future. This paper summarizes contributions and recommendations that were collected and provides guidance for future mission design, research activities, and sustainable operational radar altimetry data exploitation. Recommendations provided are fundamental for optimizing further scientific and operational advances of oceanographic observations by altimetry, including requirements for spatial and temporal resolution of altimetric measurements, their accuracy and continuity. There are also new challenges and new openings mentioned in the paper that are particularly crucial for observations at higher latitudes, for coastal oceanography, for cryospheric studies and for hydrology. The paper starts with a general introduction followed by a section on Earth System Science including Ocean Dynamics, Sea Level, the Coastal Ocean, Hydrology, the Cryosphere and Polar Oceans and the “Green” Ocean, extending the frontier from biogeochemistry to marine ecology. Applications are described in a subsequent section, which covers Operational Oceanography, Weather, Hurricane Wave and Wind Forecasting, Climate projection. Instruments’ development and satellite missions’ evolutions are described in a fourth section. A fifth section covers the key observations that altimeters provide and their potential complements, from other Earth observation measurements to in situ data. Section 6 identifies the data and methods and provides some accuracy and resolution requirements for the wet tropospheric correction, the orbit and other geodetic requirements, the Mean Sea Surface, Geoid and Mean Dynamic Topography, Calibration and Validation, data accuracy, data access and handling (including the DUACS system). Section 7 brings a transversal view on scales, integration, artificial intelligence, and capacity building (education and training). Section 8 reviews the programmatic issues followed by a conclusion

Cooperation or non-cooperation in R&D: how should research be funded? *

This article compares two research funding policies in a cooperative or non-cooperative R&D setting: subsidising private research (Spr) and subsidising public research (Spu). We show that the Spr policy induces better performance than the Spu approach in terms of overall net surplus whether firms cooperate or not in R&D. Nevertheless, subsidising public research leads to greater R&D investment overall provided that the knowledge externalities from the public to the private research sector are not too high. The Spu policy is more effective in terms of research efforts when firms cooperate and subsidies are low

R&D cooperation, proximity and distribution of public funding between public and private research sectors

In this paper, we compare the distributions of socially optimal public funding between private and public research sectors in cooperative and non-cooperative R&D settings in the presence of externalities. We show that the proportion of public funding allocated to the private sector research always increases with the level of inter-firm spillovers but decreases with the concentration of the industry. This share is smaller (larger) when firms cooperate in R&D than when they do not for high (low) spillovers. Moreover, increases in public knowledge externalities to the private sector due to a closer proximity between the two research sectors increase the share allocated to the public sector regardless of whether firms cooperate or not in R&D

R&D cooperation, proximity and distribution of public funding between public and private research sectors

International audienceIn this paper, we compare the distributions of socially optimal public funding between private and public research sectors in cooperative and non-cooperative R&D settings in the presence of externalities. We show that the proportion of public funding allocated to the private sector research always increases with the level of inter-firm spillovers but decreases with the concentration of the industry. This share is smaller (larger) when firms cooperate in R&D than when they do not for high (low) spillovers. Moreover, increases in public knowledge externalities to the private sector due to a closer proximity between the two research sectors increase the share allocated to the public sector regardless of whether firms cooperate or not in R&D

Adiponectin and adiponectin receptor genes are coexpressed during Zebrafish embryogenesis and regulated by food deprivation

International audienceAdiponectin is an adipocytokine that plays important roles in glucose and lipid homeostasis. Adiponectin binds to two types of transmembrane receptors: Adiponectin receptor (AdipoR) type 1 and 2. We isolated and characterized the two adiponectin genes (adiponectin A and B) and the three adiponectin receptors in zebrafish. In adult, adiponectin A is only detected in the kidney while adiponectin B mRNAs are widely expressed and are detected in the liver, adipose tissue, muscle, and brain. The receptors are found in many tissues such as the brain, gut, liver, adipose tissue, kidney, and ovary. Interestingly, we detect embryonic synexpression of all genes in the pharyngeal region. We observed that adiponectin B expression in adult liver is reduced while the expression of the receptors is increased in fasted fish. These data indicate that the upstream members of the Adiponectin pathway have complex expression patterns and are regulated by food deprivation in zebrafish

Invasive Drosophila suzukii facilitates Drosophila melanogaster infestation and sour rot outbreaks in the vineyards

How do invasive pests affect interactions between members of pre-existing agrosystems? The invasive pest Drosophila suzukii is suspected to be involved in the aetiology of sour rot, a grapevine disease that otherwise develops following Drosophila melanogaster infestation of wounded berries. We combined field observations with laboratory assays to disentangle the relative roles of both Drosophila in disease development. We observed the emergence of numerous D. suzukii, but no D. melanogaster flies, from bunches that started showing mild sour rot symptoms days after field collection. However, bunches that already showed severe rot symptoms in the field mostly contained D. melanogaster. In the laboratory, oviposition by D. suzukii triggered sour rot development. An independent assay showed the disease increased grape attractiveness to ovipositing D. melanogaster females. Our results suggest that in invaded vineyards, D. suzukii facilitates D. melanogaster infestation and, consequently, favours sour rot outbreaks. Rather than competing with close species, the invader subsequently permits their reproduction in otherwise non-accessible resources and may cause more frequent, or more extensive, disease outbreaks